Metformin targets mitochondrial electron transport to reduce air-pollution-induced thrombosis
Open accessAbstract
Urban particulate matter air pollution induces the release of pro-inflammatory cytokines including interleukin-6 (IL-6) from alveolar macrophages, resulting in an increase in thrombosis. Here, we report that metformin provides protection in this murine model. Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6. Targeted genetic deletion of electron transport or CRAC channels in alveolar macrophages in mice prevented particulate matter-induced acceleration of arterial thrombosis. These findings suggest metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide.
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Complex I inhibition by metformin reduces ROS-mediated IL-6 release in alveolar macrophages, preventing arterial thrombosis in mice.
“complex I inhibition by metformin also reduces ROS mediated IL-6 release in alveolar macrophages, thereby preventing arterial thrombosis in mice”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Soberanes et al. 2019
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References 50 · Cited by 131
Research works printed but not linked: 1
- Europe, W.H.O.R.O.f. (2013). In Review of evidence on health aspects of air pollution - REVIHAAP Project: Technical Report (Copenhagen: WHO Regional Office for Europe (c) World Health Organization 2013.). 27195369
- Authors
- Soberanes, S., Misharin, A. V., Jairaman, A., Morales-Nebreda, L., McQuattie-Pimentel, A. C., Cho, T., Hamanaka, R. B., Meliton, A. Y., Reyfman, P. A., Walter, J. M., Chen, C.-I., Chi, M., Chiu, S., Gonzalez-Gonzalez, F. J., Antalek, M., Abdala-Valencia, H., Chiarella, S. E., Sun, K. A., Woods, P. S., Ghio, A. J., Jain, M., Perlman, H., Ridge, K. M., Morimoto, R. I., Sznajder, J. I., Balch, W. E., Bhorade, S. M., Bharat, A., Prakriya, M., Chandel, N. S., Mutlu, G. M., & Budinger, G. R. S.
- Affiliations
- Northwestern University (US)
- University of Chicago (US)
- Environmental Protection Agency (US)
- Corresponding author
- Mutlu, Gökhan M.
- Budinger, G.R. Scott
- ORCID
- Soberanes, Saul
- Misharin, Alexander V.
- Jairaman, Amit
- Hamanaka, Robert B.
- Reyfman, Paul A.
- Walter, James M.
- Chiu, Stephen
- Antalek, Matthew
- Chiarella, Sergio E.
- Sun, Kaitlyn A.
- Woods, Parker S.
- Ghio, Andrew J.
- Jain, Manu
- Perlman, Harris
- Ridge, Karen M.
- Morimoto, Richard I.
- Sznajder, Jacob I.
- Balch, William E.
- Bhorade, Sangeeta M.
- Bharat, Ankit
- Prakriya, Murali
- Chandel, Navdeep S.
- Mutlu, Gökhan M.
- Budinger, G.R. Scott
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 29
- Issue
- 2
- Pages
- 335-347.e5
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6365216
- OpenAlex
- W2896240137
- Cited by
- 131
- References
- 50
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 15 · 2022: 17 · 2021: 27 · 2020: 21 · 2019: 8 · 2018: 1
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-02-05)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NHLBI (HL135124)
- NIAMS (AR061593)
- ATS/Scleroderma Foundation Research Grant
- DOD (PR141319)
- BD Bioscience Immunology Research Grant
- NIH (HL076139, HL125940, HL128867, AG049665, HL048129, HL071643, HL085534, ES015024, ES025644, ES026718, HL079190, HL124664, ES013995, AR064546, HL134375, CA197532)
- Thoracic Surgery Foundation
- Society of University Surgeons
- VA (BX000201, P30 CA060553)
- Core Facilities
- Center for Genetic Medicine
- Feinberg's Department of Biochemistry and Molecular Genetics
- Office of the Provost
- Office for Research
- Northwestern Information Technology
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- metformin, particulate matter pollution, arterial thrombosis, mitochondrial electron transport chain, cytochrome bc1 complex, reactive oxygen species, interleukin-6, alveolar macrophages, calcium release-activated channels, inflammation, air pollution health effects
- MeSH terms
- Air Pollution, Animals, Cell Line, Electron Transport, Humans, Lung Diseases, Male, Metformin, Mice, Inbred C57BL, Mitochondria, Thrombosis, Interleukin-6, Cytokines, Macrophages, Alveolar, Reactive Oxygen Species, Mice, Particulate Matter
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